Ginsenoside Rg1 treatment alleviates renal fibrosis by inhibiting the NOX4–MAPK pathway in T2DM mice
Pengmin Ji,
Qifeng Shi,
Yan Liu,
Min Han,
Yong Su,
Ran Sun,
Huimin Zhou,
Weizu Li,
Weiping Li
Affiliations
Pengmin Ji
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Qifeng Shi
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Yan Liu
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Min Han
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Yong Su
Department of Pharmacy, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Ran Sun
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Huimin Zhou
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Weizu Li
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Weiping Li
Department of Pharmacology, School of Basic Medical Sciences, Key Laboratory of Anti-inflammatory and Immunopharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Diabetic kidney disease (DKD) is a severe complication of type 2 diabetes mellitus (T2DM). However, the pathogenesis of DKD remains unclear, and effective treatment strategies are still lacking. Ginsenoside Rg1 (Rg1) has been reported to improve DKD, but the mechanism is unclear. NADPH oxidase 4 (NOX4) is an essential reactive oxygen species (ROS) source in the kidney. The mitogen-activated protein kinase (MAPK) signaling may exacerbate renal fibrosis. Therefore, we hypothesized that Rg1 might alleviate renal injury and fibrosis by inhibiting NOX4 and MAPK signaling in T2DM-induced DKD. We found that Rg1 significantly improves lipid deposition, fibrosis, and ROS production and reduces NOX4, p22phox, p47phox, p-ERK, p-JNK, and p-P38 MAPK expressions in the T2DM mice kidneys. We also found that the high-fat diet treatment in mice and the palmitate (PA) and PA + HG (high glucose) exposure in human mesangial cells could significantly induce lipid deposition, ROS production, fibrosis, and the activation of NOX4–MAPK signaling. The results suggest that high lipid and glucose may play a significant role in DKD progression, while Rg1 may attenuate renal fibrosis by inhibiting NOX4–MAPK signaling.